Chimeric Receptor Polypeptide for Autoimmune B Cell Elimination
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Solution Overview
Problem
Current treatments for autoimmune diseases, such as lupus and rheumatoid arthritis, lack effective cures and often rely on immunosuppressive drugs, with B cells playing a significant role in disease pathology but being challenging to target effectively.
Innovation Solution
Development of chimeric receptor polypeptides and chimeric antigen receptors that can be administered to patients, specifically designed to modulate signaling in CD11c+T-bet+ B cells by binding to specific antigens and inducing proteolytic cleavage, activating transcriptional control units to express therapeutic receptors, thereby reducing or eliminating these cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive drugs are used to treat autoimmune diseases, then disease symptoms can be managed, but there is no cure and the treatment lacks effectiveness
Solution Approach 1:
The patent extracts and eliminates pathogenic B cells (CD11c+T-bet+ B cells) from the patient's body using chimeric antigen receptor (CAR) T cells that specifically target and kill these cells. This extraction approach removes the root cause of autoimmune disease rather than merely suppressing symptoms, achieving a potential cure rather than just management.
Solution Approach 2:
The patent changes the parameter of B cell population by selectively reducing CD11c+T-bet+ B cells while maintaining other beneficial B cell functions. This targeted parameter change allows elimination of pathogenic cells without complete immunosuppression, improving treatment effectiveness while preserving immune function.
2Reliability
If B cells are targeted for treatment, then autoimmune disease pathology can be addressed, but B cells are challenging to target effectively
Solution Approach 1:
The patent applies local quality by creating CAR T cells with specific antigen binding domains that recognize unique markers (CD11c and T-bet) on pathogenic B cells. This localized targeting approach ensures that only the specific pathogenic B cell population is affected, making the targeting effective and precise rather than diffuse.
Solution Approach 2:
The patent uses composite CAR T cell structures combining multiple functional elements: antigen binding domains, transmembrane domains, and intracellular signaling domains. This composite design integrates multiple functions into a single targeting system, overcoming the difficulty of effective B cell targeting by creating a multi-component solution.
3Adaptability or versatility
If traditional immunosuppressive treatments are used, then treatment can be administered, but the approach lacks novelty and therapeutic innovation
Solution Approach 1:
Instead of suppressing the immune system to treat autoimmune disease (traditional approach), the patent inverts the strategy by actively enhancing specific immune responses through CAR T cells that selectively attack pathogenic B cells. This inversion transforms the treatment from passive immunosuppression to active targeted elimination, achieving both novelty and improved effectiveness.
Solution Approach 2:
The patent employs self-service by designing CAR T cells that autonomously recognize and eliminate pathogenic B cells through their unique antigen binding domains. The system serves itself by using the patient's own immune cells (T cells) that have been engineered to perform the therapeutic function, eliminating the need for external immunosuppressive drugs and achieving therapeutic innovation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The approach potentially alleviates autoimmune disorder symptoms by specifically targeting and reducing the population of pathogenic B cells, offering a novel therapeutic strategy beyond traditional immunosuppression.
Implementation Method 1
contacting the cell with a CD11c+T-bet+ B cell expressing the first antigen on its surface, wherein the contacting induces cleavage at the proteolytic site, thereby releasing the intracellular domain
Implementation Method 2
releasing the intracellular domain result in the transcriptional control unit's activation of the transcriptional control element. The transcriptional control element is operably linked to the nucleic acid sequence encoding the chimeric antigen receptor polypeptide, which results in expression of the chimeric antigen receptor polypeptide
Implementation Method 3
the chimeric antigen receptor polypeptide comprises a second antenna binding domain capable of binding to a second antenna present on the CD11c+T-bet+ Bet cell
Data Source
AI summary
This disclosure provides for chimeric receptor polypeptides where upon binding of a first antigen to the antigen binding domain triggers a proteolytic cleavage and upregulation of a chimeric antigen receptor, wherein the chimeric antigen receptor binds to a second antigen. The first and second antigens are present on a population of B cells known as Autoimmune- or Age-related B cells or CD11c+T-bet+ B cells. The present disclosure includes methods and compositions for reducing or eliminating ABCs through the binding of the chimeric antigen receptor, and thus controlling or eliminating autoimmune disease.